Natural flavonoids as potential multifunctional agents in prevention of diabetic cataract

Cataract is one of the earliest secondary complications of diabetes mellitus. The lens is a closed system with limited capability to repair or regenerate itself. Current evidence supports the view that cataractogenesis is a multifactorial process. Mechanisms related to glucose toxicity, namely oxidative stress, processes of non-enzymatic glycation and enhanced polyol pathway significantly contribute to the development of eye lens opacity under conditions of diabetes. There is an urgent need for inexpensive, non-surgical approaches to the treatment of cataract. Recently, considerable attention has been devoted to the search for phytochemical therapeutics. Several pharmacological actions of natural flavonoids may operate in the prevention of cataract since flavonoids are capable of affecting multiple mechanisms or etiological factors responsible for the development of diabetic cataract. In the present paper, natural flavonoids are reviewed as potential agents that could reduce the risk of cataract formation via affecting multiple pathways pertinent to eye lens opacification. In addition, the bioavailability of flavonoids for the lens is considered

Physiological controls of bacterial spinae production in complex medium and their value as indicators of spina function

Complex medium is rendered alkaline by the growth of marine pseudomonad D71, and in such a medium spinae are produced towards the end of log phase when the pH has increased over 7.5. Spinae production is unaffected by changes in oxygen tension and illumination but controlled by interactions of pH, salt concentration, and temperature. Under optimal laboratory conditions for growth a culture is partially spined but it becomes increasingly spined as growth temperature or pH is increased or ionic concentration decreased. By contrast, flagella are produced at low temperatures and pH, suggesting that spinae function in an opposite sense to flagella accommodating the bacterium to its environment. The conditions controlling spinae production are discussed in the context of possible spina function. </jats:p

Expression and function of beta-glucuronidase in pancreatic cancer: potential role in drug targeting

Improvement of non-surgical strategies is a pivotal task in the treatment of pancreatic cancer. Response to treatment with most anticancer agents has been very poor, probably due to insufficient drug concentration in tumor tissue. Increased response rates during chemotherapy might be achieved by dose escalation; however, this approach is often hampered by severe side effects. One strategy to overcome these adverse effects is application of nontoxic glucuronide prodrugs from which the active moiety is released by beta-glucuronidase within or near the tumor. The use of glucuronide prodrugs in pancreatic cancer requires increased expression of the enzyme in the diseased tissue, a problem that has not been addressed so far. We therefore investigated function and expression of beta-glucuronidase in tissue samples from human healthy pancreas (n = 7) and pancreatic adenocarcinoma (n = 8 ), respectively. Comparing the ability of tissue homogenates to cleave the standard substrate 4-methylumbelliferyl-beta-D-glucuronide, we found a significantly increased specific beta-glucuronidase activity (P < 0.05) in pancreatic cancer (median: 133; 75% percentile: 286; 25% percentile: 111 nmol/mg per h) as compared to healthy pancreas (median: 74; 75% percentile: 113; 25% percentile: 71 nmol/mg per h). Enzyme kinetic experiments with the model prodrug N-[4-beta-glucuronyl-3-nitrobenzyloxycarbonyl] doxorubicin (HMR 1826) demonstrated bioactivation of HMR 1826 by pancreatic beta-glucuronidase. Enzymatic activity was found to be closely related to enzyme contents (r = 0.87) as assessed by Western blot analysis. Our data indicate that increased beta-glucuronidase activity in pancreatic cancer seems to be due to an elevated steady-state level of the protein. This may be the basis for new therapeutic strategies in treatment of pancreatic carcinoma by using glucuronide prodrugs of anticancer agents

Five new galactolipids from the freshwater microalga Porphyridium aerugineum and their nitric oxide inhibitory activity

Chemical investigation of the freshwater rhodophyte microalga Porphyridium aerugineum led to the isolation of five new galactolipids, namely, (2S)-1-O-eicosapentaenoyl-2-O-arachidonoyl-3-O-\u3b2-d-galactopyranosylglycerol (1), (2S)-1-O-eicosapentaenoyl-2-O-linoleoyl-3-O-\u3b2-d-galactopyranosylglycerol (2), (2S)-1-O-arachidoyl-2-O-palmitoyl-3-O-(\u3b2-d-galactopyranosyl-6-1\u3b1-d-galactopyranosyl)-glycerol (6), (2S)-1-O-eicosapentaenoyl-2-O-arachidoyl-3-O-(\u3b2-d-galactopyranosyl-6-1\u3b1-d-galactopyranosyl)-glycerol (7), and (2S)-1-O-eicosapentaenoyl-2-O-linoleoyl-3-O-(\u3b2-d-galactopyranosyl-6-1\u3b1-d-galactopyranosyl)-glycerol (8) together with five known galactolipids. The stereo-structures of all new galactolipids were elucidated by spectroscopic analyses and both enzymatic and chemical degradation methods. This is the first report of galactolipids from P. aerugineum. The newly isolated galactolipids showed strong and dose-dependent nitric oxide (NO) inhibitory activity against lipopolysaccharide-induced NO production in RAW264.7 macrophage cells. Both galactolipids 1 and 2 possessed stronger NO inhibitory activity than N G-methyl-l-arginine acetate salt, a well-known NO inhibitor used as a positive control. Further study suggested that these galactolipids inhibit NO production through downregulation of inducible nitric oxide synthase expression.Peer reviewed: YesNRC publication: Ye

Fifteen Years After Sleeve Gastrectomy: Weight Loss, Remission of Associated Medical Problems, Quality of Life, and Conversions to Roux-en-Y Gastric Bypass—Long-Term Follow-Up in a Multicenter Study

Abstract Purpose Since 2014, sleeve gastrectomy (SG) has been the most frequently performed bariatric-metabolic operation worldwide (2018: 386,096). There are only a few studies reporting a long-term follow-up (up to 11 years) available today. The aim of this study was to evaluate the long-term outcome of SG with a follow-up of at least 15 years regarding weight loss, remission of associated medical problems (AMP), conversions, and quality of life (QOL). Setting Multicenter cross-sectional study; university hospital. Methods This study includes all patients who had SG before 2005 at the participating bariatric centers. History of weight, AMP, conversions, and QOL were evaluated by interview at our bariatric center. Results Fifty-three patients met the inclusion criteria of a minimal follow-up of 15 years. Weight and body mass index at the time of the SG were 136.8kg and 48.7kg/m2. Twenty-six patients (49.1%) were converted to Roux-en-Y gastric bypass (RYGB) for weight regain and gastroesophageal reflux within the follow-up period. Total weight loss after 15 years was 31.5% in the non-converted group and 32.9% in the converted group. Remission rates of AMP and QOL were stable over the follow-up period. Conclusion Fifteen years after SG, a stable postoperative weight was observed at the cost of a high conversion rate. Patients converted to RYGB were able to achieve further weight loss and preserve good remission rates of AMP. SG in patients without the need of a conversion to another bariatric-metabolic procedure may be considered effective. Careful preoperative patient selection is mandatory when performing SG. Graphical abstract </jats:sec

Obesity Surgery / Fifteen years after sleeve gastrectomy: weight loss, remission of associated medical problems, quality of life, and conversions to Roux-en-Y gastric bypass - long-term follow-up in a multicenter study

Purpose Since 2014, sleeve gastrectomy (SG) has been the most frequently performed bariatric-metabolic operation worldwide (2018: 386,096). There are only a few studies reporting a long-term follow-up (up to 11 years) available today. The aim of this study was to evaluate the long-term outcome of SG with a follow-up of at least 15 years regarding weight loss, remission of associated medical problems (AMP), conversions, and quality of life (QOL). Setting Multicenter cross-sectional study; university hospital. Methods This study includes all patients who had SG before 2005 at the participating bariatric centers. History of weight, AMP, conversions, and QOL were evaluated by interview at our bariatric center. Results Fifty-three patients met the inclusion criteria of a minimal follow-up of 15 years. Weight and body mass index at the time of the SG were 136.8kg and 48.7kg/m2. Twenty-six patients (49.1%) were converted to Roux-en-Y gastric bypass (RYGB) for weight regain and gastroesophageal reflux within the follow-up period. Total weight loss after 15 years was 31.5% in the non-converted group and 32.9% in the converted group. Remission rates of AMP and QOL were stable over the follow-up period. Conclusion Fifteen years after SG, a stable postoperative weight was observed at the cost of a high conversion rate. Patients converted to RYGB were able to achieve further weight loss and preserve good remission rates of AMP. SG in patients without the need of a conversion to another bariatric-metabolic procedure may be considered effective. Careful preoperative patient selection is mandatory when performing SG